It is proposed to test the hypothesis that increased estrogen activity is a factor in the generalized fluid retention of right heart failure, and (acting locally) in the pulmonary edema of left heart failure. Using radioimmunoassay methods we shall measure arterial plasma concentrations of specific estrogens and estrogen conjugates in cases of right heart failure. Comparison of estrogen levels before and after conventional treatment will indicate whether any elevated levels are related to the fluid retention. Measuring specific estrogens simultaneously in plasma and urine will determine whether increased plasma estrogen levels are associated with decreased renal clearances of these estrogens. In the dog, the lung is active in the hydrolysis of estrogen conjugates to physiologically-active free (unconjugated) estrogens. By measuring free estrogens simultaneously in right ventricle and peripheral artery plasma and calculating the % extraction by the lungs we shall determine whether this is also true for the human. An increase in the (negative) % extraction in left heart failure as compared with controls, associated with an elevation of peripheral artery levels, would be consistent with our hypothesis that lung tissue was exposed to increased concentrations of physiologically-active estrogens, and that this could be associated with local fluid accumulation (pulmonary edema). Using similar methods and hepatic vein catheterization we shall determine whether decreased splanchnic extraction of free estrogens as compared with controls contributes to the elevation of plasma free estrogens in heart failure. We will determine whether the estrogen content of the pleural effusion of heart failure is higher than pleural effusion due to the causes. Finally we will determine estrone metabolic clearance rates (MCR) and blood production rates (BPR) in heart failure and compare them with controls. A decreased MCR but maintained BPR would be consistent with our hypothesis.